Role of IL-5 in the innate immune system and disease control

Abstract Mature B cells expressing surface IgM as B cell receptor (BCR) consist of two B-cell subpopulations, B-1 and B-2 cells that regulate innate and acquired immunity, respectively. B-1 cells become natural Ig-producing plasma cells in response to natural ligands or self-antigens. Mature B-2 cells proliferate and differentiate into Ig-producing plasma cells under the influence of T helper (Th) cells. Antigen stimulation of B-2 cells induces class switch recombination (CSR) from IgM to other isotypes that is regulated by cytokines and activation-induced cytidine deaminase (AID). IL-5 activates B cells and eosinophils and regulates the innate and acquired immune response. IL-5 stimulates innate B-1 cells and induces the homeostatic proliferation, survival and differentiation of B cells leading to increased secretion of natural antibody. IL-5Rα-deficient mice show the impaired contact sensitivity that is mediated by activated T cells and IgM antibody produced by B-1 cells. IL-5 induces AID and Blimp-1 expression in activated B-2 cells leading to μ to γ1 CSR and IgG1 production. In contrast, IL-4 does not induce μ to γ1 CSR in anti-CD38-activated B-2 cells. Intriguingly, the costimulation of anti-CD38-activated B-2 cells with 8-mercaptoguanosine and IL-4 induces μ to γ1 CSR and IgG1 production, suggesting that unidentified factor(s) is/are required together with AID to complete CSR. We will discuss the role of IL-5 in the innate immune system and disease control, particularly the regulation of contact sensitivity and chronic inflammation through B-1 cell activation and IgM production.